The in vivo microdialysis technique has been developed to monitor dynamic extracellular neurotransmitter levels in the Rhesus monkey brain. This technique enables the characterization of the neurochemical neuropharma- cological correlates, of cortical regulation of subcortical structures, and frontal and temporal lobe functional interaction. We have developed a guide cannula system which aids in the accurate and repeatable place- ment of dialysis probes in both sedate and awake behaving monkeys. Initial studies with the caudate nucleus and prefrontal cortex. However, DA was much lower and more difficult to detect in the cortex than in the caudate. At present measurements of DA in the cortex is so unreliable planned experimentation to examine DA alone does not merit consideration. However, it is possible to examine the effects of manipulating DA and observe how this might effect levels of other transmitter locally and other interconnected neural regions. We confirmed that the DA monitored was neuronally released from the synapse rather than released from damaged synaptic vesicles from insertions of the microdialysis probe. Pharmacological manipulation by infusion of amphetamine and cocaine through the dialysis probe resulted in dramatically increased DA levels in both the cortex and the striatum. Remarkably, this increase could be seen in the cortex even when prior to the amphetamine or cocaine infusion baseline DA levels were below detection. Recently, we have been able to monitor some of the amino acids, such as, glutamate, aspartate, and gaba, in our dialysate samples. In contrast DA these were more consistantly detected in the cortex and like dopamine increased significantly with amphetamine and cocaine infusion. Because of the dramatic changes we found with cortical dA we examined what effect increasing/decreasing cortical dopamine would have on subcortical targets of the mesocortical dopamine system, such as the caudate nucleus. Prefrontal cortical infusion of amphetamine or cocaine resulted in significant reduction in striatal DA release. Glutamate infusion in the prefrontal cortex also resulted in caudate. TTX was infused into the prefrontal cortex to prevent broad spectrum impulse dependant neuronal activity. Kynurenic acid was infused into the cortex to block glutamertergic transmission on caudate dopamine and amino acids.